Department of Genetics and Institute of Biomedicine, University of Barcelona, E-08028 Barcelona, Catalonia, Spain.
Proc Natl Acad Sci U S A. 2011 Feb 15;108(7):2813-8. doi: 10.1073/pnas.1012090108. Epub 2011 Jan 31.
The Wingless/Integrated (Wnt) signaling pathway controls multiple events during development and homeostasis. It comprises multiple branches, mainly classified according to their dependence on β-catenin activation. The Wnt/β-catenin branch is essential for the establishment of the embryonic anteroposterior (AP) body axis throughout the phylogenetic tree. It is also required for AP axis establishment during planarian regeneration. Wnt/β-catenin-independent signaling encompasses several different pathways, of which the most extensively studied is the planar cell polarity (PCP) pathway, which is responsible for planar polarization of cell structures within an epithelial sheet. Dishevelled (Dvl) is the hub of Wnt signaling because it regulates and channels the Wnt signal into every branch. Here, we analyze the role of Schmidtea mediterranea Dvl homologs (Smed-dvl-1 and Smed-dvl-2) using gene silencing. We demonstrate that in addition to a role in AP axis specification, planarian Dvls are involved in at least two different β-catenin-independent processes. First, they are essential for neural connectivity through Smed-wnt5 signaling. Second, Smed-dvl-2, together with the S. mediterranea homologs of Van-Gogh (Vang) and Diversin (Div), is required for apical positioning of the basal bodies of epithelial cells. These data represent evidence not only of the function of the PCP network in lophotrocozoans but of the involvement of the PCP core elements Vang and Div in apical positioning of the cilia.
无翅型/整合素(Wnt)信号通路控制着发育和稳态过程中的多个事件。它包含多个分支,主要根据其对β-连环蛋白激活的依赖性进行分类。Wnt/β-连环蛋白分支对于在整个系统发育树中建立胚胎前后(AP)身体轴至关重要。它也是扁形虫再生过程中 AP 轴建立所必需的。Wnt/β-连环蛋白非依赖性信号转导包含几个不同的途径,其中研究最广泛的是平面细胞极性(PCP)途径,它负责上皮片中细胞结构的平面极化。Dvl(Dishevelled)是 Wnt 信号的枢纽,因为它调节和引导 Wnt 信号进入每个分支。在这里,我们使用基因沉默分析了 Schmidtea mediterranea Dvl 同源物(Smed-dvl-1 和 Smed-dvl-2)的作用。我们证明,除了在 AP 轴特化中的作用外,扁形虫 Dvls 还参与至少两个不同的β-连环蛋白非依赖性过程。首先,它们通过 Smed-wnt5 信号对于神经连接是必不可少的。其次,Smed-dvl-2 与 S. mediterranea 的 Van-Gogh(Vang)和 Diversin(Div)同源物一起,对于上皮细胞基底体的顶端定位是必需的。这些数据不仅代表了 PCP 网络在环节动物中的功能证据,还代表了 PCP 核心元件 Vang 和 Div 在纤毛顶端定位中的参与。